polymorphism. PL contributed his expertise on vitamin D deficiency and
consequences for bone loss, fractures and therapeutic implications. CP
contributed his clinical expertise on patients with MS. All authors
read and contributed to the manuscript.

Abstract

MS is a chronic, immune-mediated inflammatory and neurodegenerative
disease of the central nervous system (CNS), with an etiology that is
not yet fully understood. The prevalence of MS is highest where
environmental supplies of vitamin D are lowest. It is well recognized
that the active hormonal form of vitamin D,
1,25-dihydroxyvitamin D (1,25-(OH)2D), is a natural immunoregulator
with anti-inflammatory action. The mechanism by which vitamin D
nutrition is thought to influence MS involves paracrine or autocrine
metabolism of 25OHD by cells expressing the enzyme 1-OHase in
peripheral tissues involved in immune and neural function.
Administration of the active metabolite 1,25-(OH)2D in mice and rats
with experimental allergic encephalomyelitis (EAE, an animal model of
MS) not only prevented, but also reduced disease activity. 1,25-(OH)2D
alters dendritic cell and T-cell function and regulates macrophages in
EAE. Interestingly, 1,25-(OH)2D is thought to be operating on CNS
constituent cells as well.

Vitamin D deficiency is caused by insufficient sunlight exposure or
low dietary vitamin D3 intake. Subtle defects in vitamin D metabolism,
including genetic polymorphisms related to vitamin D, might possibly
be involved as well. Optimal 25OHD serum concentrations, throughout
the year, may be beneficial for patients with MS, both to obtain
immune-mediated suppression of disease activity, and also to decrease
disease-related complications, including increased bone resorption,
fractures, and muscle weakness.